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Preclinical models in ophthalmic oncology-a narrative review

Annals of Eye Science 2022年第2期7卷 59-73页

作者： Daria Lehrmann Nasrin Refaian Michael Simon alexander c.rokohl Ludwig M.Heindl Department of Ophthalmology Faculty of Medicine and University Hospital CologneUniversity of CologneCologneGermany center for Integrated Oncology(cIO) Aachen-Bonn-Cologne-DüsseldorfCologneGermany

Objective:This review serves as a comprehensive description and summary of currently available preclinical models of three tumors in ophthalmic oncology:conjunctival melanoma(cM),uveal melanoma(UM),and ***:Malignant melanomas are the most common tumors of the eye in adults,most often localized in the uvea and *** the primary tumor can be successfully eliminated in many cases,nearly one in two UMs-and one in three cMs-are fatal to the patient due to *** therapies for metastatic uveal and cMs are unfortunately still not available,so there is an urgent need for new therapeutic strategies to improve prognosis quoad vitam and prolong the survival of melanoma *** widely known tumor of the eye is retinoblastoma,which is the most common pediatric ocular malignancy,occurring in approximately 1 in 15,000-18,000 live ***,it is considered well treatable,with a survival rate of approximately 90%at 3 years,although fatal if *** a long time,enucleation was also considered the treatment of choice,with bilateral cases having one eye irradiated and the eye with the more advanced tumor *** the 1990s,however,systemic chemotherapy has been predominantly used to preserve the quality of life and vision of young patients,although the cellular activity of the retinoblastoma often remains after treatment with chemotherapeutic *** of the disease is immensely depending on the stage and time of diagnosis and is varying between countries due to different developmental status of health care ***:We review recent advances in the available literature on established preclinical models in cM,UM,and *** addition,we discuss the advantages and limitations of these models and provide an overview of current alternatives to animal testing in preclinical ***:In the case of all three diseases,further research is needed for improved therapeutic ***

关键词： conjunctival melanoma(cM) uveal melanoma(UM) retinoblastoma ocular tumor preclinical models

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A modified 3D stereophotogrammetry-based distraction test for assessing lower eyelid tension

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International Journal of Ophthalmology(English edition) 2022年第11期15卷 1757-1764页

作者： Xiao-Yi Hou alexander c.rokohl Marius M.Meinke Sen-Mao Li Ming Lin Ren-Bing Jia Yong-Wei Guo Ludwig M.Heindl Department of Ophthalmology West China Hospital of Sichuan UniversityChengdu 610041Sichuan ProvinceChina Department of Ophthalmology Faculty of Medicine and University Hospital CologneUniversity of CologneCologne 50937Nordrhein-WestfalenGermany Department of Ophthalmology Ninth People's HospitalShanghai Jiao Tong University School of MedicineShanghai 200011China Eye center Second Affiliated HospitalSchool of MedicineZhejiang UniversityHangzhou 310009Zhejiang ProvinceChina center for Integrated Oncology(cIO)Aachen-Bonn-cologne-Duesseldorf Cologne 50937Nordrhein-WestfalenGermany

AIM: To investigate the reliability of a modified threedimensional distraction test(3D-DT) and three-dimensional pinch test(3D-PT) for assessing lower eyelid tension(LET).METHODS: A cross-sectional study was conducted among 97 volunteer s including 97 eyelids with no history of trauma, tumor, or reconstructive surgeries. Six three-dimensional photographs were acquired for each par ticipant, including two photographs obtained in a neutral position(NP), two using a modified 3D-DT with a 15.9-grammes stainless steel eyelid hook performed, and two using ***: The mean absolute differences between NP, 3D-DT, and 3D-PT measurements varied between 0.07 and 7.42, 0.10 and 13.10, and 0.07 and 15.97, respectively;technical error of measurement varied between 0.05 and 7.81, 0.09 and 10.19, and 0.07 and 12.47, respectively;and relative error measurements varied between 0.10% and 11.50%, 0.16% and 30.51%, and 0.11% and 38.75%, respectively. For intra-rater reliability, the intraclass correlation coefficients(Iccs) were more than 0.80 in seven out of eight measurements obtained in the NP and 3D-DT, whereas those obtained in the 3D-PT were as low as less than 0.30 by rater 1;the Iccs of all the measurements obtained in all the positions(NP, 3D-DT, and 3D-PT) were more than 0.80 by rater 2. For inter-rater reliability six out of eight NP and 3D-DT measurements had an Icc greater than 0.80, whereas those of 3D-PT measurements were less than 0.30. For intra-method reliability, the Iccs of all the NP measurements were more than 0.87, whereas those of the six 3D-DT measurements and four 3D-PT measurements were more than ***: Our study results prove that the modified 3D-DT, which involves the use of an eyelid hook, can be a highly reliable method for evaluating LET. Furthermore, this novel and simple method may be utilized as the basis for further investigation and routine pre-and postoperative clinical evaluation.

关键词： three-dimensional distraction test lower eyelid tension standard-weighted eyelid hook threedimensional stereophotogrammetry landmark system

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Pterygium:new insights into risk factors?

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Annals of Eye Science 2022年第4期7卷 1-3页

作者： alexander c.rokohl Ludwig M.Heindl Department of Ophthalmology University of CologneFaculty of Medicine and University Hospital of CologneCologneGermany center for Integrated Oncology(cIO)Aachen-Bonn-cologne-Düsseldorf CologneGermany

Introduction The word pterygium comes from two Greek words:(pteryx)meaning wing and(pterygion)fin(1-3).Pterygium,one of the most common benign tumors of the ocular surface,is a focal fibrovascular proliferation of conjunctival tissue onto the cornea(1-6).The pterygium is usually triangular in shape and localized in the nasal palpebral fissure(1-6).Histopathologically,there is usually a nonkeratinizing epithelium and loss of goblet cells(4).Some cases show also the development of a multilayered keratinizing squamous *** features include thickened collagen fibers,numerous vascular incisions,and pathognomonic elastoid ***,chronic inflammation,such as lymphocytic infiltration,can also be seen(2-6).Furthermore,the head of the pterygium,which is firmly fused to the cornea,can also grow into the upper corneal layers and fragment Bowman’s lamella(1-4).

关键词： Bowman fused epithelium

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Targeted therapy for malignant ocular melanomas

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Annals of Eye Science 2021年第1期6卷 46-52页

作者： Rahul Arvo Jonas alexander c.rokohl Ludwig M.Heindl Department of Ophthalmology Faculty of Medicine and University Hospital CologneUniversity of CologneCologneGermany center for Integrated Oncology(cIO)Aachen-Bonn-cologne-Dusseldorf CologneGermany

In a comprehensive literature review,PubMed,Embasem and Web of Science were searched for studies examining targeted therapy of ocular malignant melanomas to present and discuss targeted therapy treatment options of ocular tumors,mainly conjunctival and uveal melanoma(UM).conjunctival malignant melanomas showed similarities in clinical and genetic aspects with cutaneous *** therapies with checkpoint inhibitors already established for cutaneous melanomas may be a treatment option for conjunctival malignant melanomas with shared *** targeted therapies are for example checkpoint inhibitors like pembrolizumab or *** a corollary,due to marked differences in clinics and genetics between UMs and conjunctival melanomas(cMs)or cutaneous melanomas,it has remained elusive whether the available possibilities of molecular targeted therapy will be an option for the therapy of metastasizing *** novel ways of treating UM are being *** or the inoculation of dendritic cells with tumorous RNA or sunitinib in combination with cisplatin and or tamoxifen may be used in future to treat *** cM are treatable using targeted therapies,UM have not been researched enough to find working targeted therapy *** research has to be done in order to find acceptable treatment options.

关键词： conjunctival melanoma(cM) uveal melanoma(UM) retinoblastoma ocular tumor targeted therapies

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Three-dimensional anthropometry in periorbital region

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Annals of Eye Science 2021年第1期6卷 53-63页

作者： Yongwei Guo alexander c.rokohl Ming Lin Ludwig M.Heindl Eye center Second Affiliated HospitalSchool of MedicineZhejiang UniversityHangzhouChina Department of Ophthalmology University of CologneFaculty of Medicine and University Hospital CologneCologneGermany Department of Ophthalmology Ninth People’s HospitalShanghai Jiao Tong University School of MedicineShanghaiChina center for Integrated Oncology(cIO)Aachen-Bonn-cologne-Duesseldorf CologneGermany

Anthropometry can analyze the size,weight,and proportion of the human body objectively and quantitatively to supplement the visual *** non-invasive three-dimensional(3D)anthropometric techniques have been applied to assess soft tissues’3D morphology in the clinical *** them,non-invasive stereophotogrammetry and laser scanning techniques are becoming increasingly popular in craniofacial surgery and plastic *** have been applied for craniofacial growth estimation and morphometric investigation,genetic and acquired malformation diagnosis,as well as orthodontic or surgical treatment arrangement and outcome ***,few studies have been published for assessing the 3D morphology of soft tissues in the periorbital *** paper reviews the studies involving the application and evaluation of the increasingly popular 3D photogrammetry in the periorbital *** studies proposed detailed and standardized protocols for three-dimensionally assessing linear,curvilinear,angular,as well as volumetric measurements,and verified its high reliability in the periorbital region(even higher than caliper-derived direct measurements).In the future,reliable and accurate 3D imaging techniques,as well as standardized analyzing protocols,may find applications in following up morphological growth,preoperatively diagnosing and assessing patient periorbital conditions,planning surgical procedures,postoperatively evaluating treatment outcomes of a specific procedure,and comparing the differences in surgical results between various procedures,studies,as well as populations.

关键词： Three-dimensional(3D) photogrammetry periorbital soft tissue eye face

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Ocular surface and tear film changes after eyelid surgery

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Annals of Eye Science 2021年第1期6卷 64-74页

作者： Wanlin Fan alexander c.rokohl Yongwei Guo Ludwig M.Heindl Department of Ophthalmology Faculty of Medicine and University Hospital CologneUniversity of CologneCologneGermany Eye center Second Affiliated HospitalSchool of MedicineZhejiang UniversityHangzhouChina center for Intergrated Oncology(cIO) Aachen-Bonn-Cologne-DuesseldorfCologneGermany

Eyelid surgery is widely and extensively used in facial plastic and reconstructive *** are many categories of eyelid surgeries,the most common of which include blepharoplasty,ptosis surgery,and eyelid *** many cases,these procedures are combined,and there are many different techniques for each type of *** eyelid blepharoplasty usually includes the excision of skin,preseptal orbicularis oculi muscle,and orbital *** methods of lower eyelid blepharoplasty are the skin-muscle flap,the skin flap,and the *** surgery is mainly divided into three types:transcutaneous,transconjunctival,and sling *** often used the Hughes or cutler-Beard Bridge Flaps in eyelid *** types and methods of surgery have their own advantages and disadvantages,and postoperative complications may ***,postoperative complications of eyelid surgeries,such as dry eye symptoms,should be taken into serious *** literature involving these complaints can be found in PubMed by searching the terms“dry eye”,“eyelid”,“surgery”,and other related ***,various ocular surface and tear film alterations may be detected using the Ocular Surface Disease Index(OSDI),tear film breakup time,Schirmer test,fluorescein staining,and lissamine green staining after various eyelid *** dry eye disease is prevalent in the general population,it is more urgent to figure out what we can learn from these *** exploration in this field may help surgeons to choose a better surgical method and give an accurate evaluation of the postoperative effect.

关键词： Ocular surface tear film dry eye syndrome(DES) eyelid surgery

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Periocular basal cell carcinoma-current treatment concepts

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Annals of Eye Science 2021年第2期6卷 62-77页

作者： Yongwei Guo alexander c.rokohl Adam Kopecky Ludwig M.Heindl Eye center Second Affiliated HospitalSchool of MedicineZhejiang UniversityHangzhouChina Department of Ophthalmology University of CologneFaculty of Medicine and University Hospital CologneCologneGermany clinic of Ophthalmology University Hospital OstravaOstravaCzech Republic Faculty of Medicine Department of Craniofacial SurgeryUniversity of OstravaOstravaCzech Republic center for Integrated Oncology(cIO)Aachen-Bonn-cologne-Duesseldorf CologneGermany

Basal cell carcinoma(Bcc)is by far the most common human skin *** caucasians,Bccs account for around 90%of periocular ***,periocular Bccs are usually neglected due to their slow and painless growth,unless presenting complaints,e.g.,large size,bleeding,recurrent infections of the tumor,or secondary symptoms resulting from adjacent structures involvement as epiphora,limited eye globe motility as well as globe ***,although the tumor can usually be cured with local excision,local recurrence can occur in up to 20%of eyelid Bcc *** Bccs of the eyelid show a poorer overall prognosis than the primary *** addition,the management of advanced diseases,such as orbital or intracranial invasion as well as metastatic lesions,is challenging and often involves a multidisciplinary *** this paper,we reviewed the recent research progress of pathogenesis,clinical presentation,and therapeutics of periocular *** introduced the molecular pathogenesis of Bccs[multi-step ultraviolet(UV)-induced carcinogenesis model,genetic predisposition,and epigenetic changes],clinical classification,and tumor-node-metastasis(TNM)clinically stage of eyelid skin *** also emphasized the treatment of Bccs,i.e.,surgical resection,oculoplastic reconstruction,and alternative therapies(radiation therapy,systemic therapy,topical therapy,and prophylactic therapy).In the end,we proposed that considering the possible iatrogenic damage to the surface of the eye by surgical excision,the treatment of periocular Bccs is recommended to be performed by or in the presence of an oculoplastic surgeon.

关键词： Periocular basal cell carcinoma(periocular Bcc) pathogenesis diagnosis therapeutics precaution

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Bioengineered dermal substitutes for periocular defects

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Annals of Eye Science 2021年第2期6卷 45-50页

作者： Adam Kopecký Jan Němčanský Vladimir Kratky alexander c.rokohl Ludwig M.Heindl Ophthalmology clinic University Hospital OstravaOstravaCzech Republic Department of Ophthalmology University of CologneFaculty of Medicine and University Hospital CologneCologneGermany Faculty of Medicine Department of Craniofacial SurgeryUniversity of OstravaOstravaCzech Republic Department of Ophthalmology Kingston Health Sciences CentreQueen’s UniversityKingstonONCanada Department of Ophthalmology 1st Medical FacultyCharles UniversityPragueCzech Republic Department of Ophthalmology Center for Integrated Oncology(CIO)Aachen-Bonn-Cologne-DuesseldorfCologneGermany

Bioengineered materials are used as a substitute in many fields of medicine,especially in plastic surgery and in *** ophthalmic plastic surgery they can be used for covering large tissue defects or as a tarsal plate substitute,in cases when it is not possible to use conventional surgical *** have searched PubMed and Web of Science scientific *** can generally categorize skin substitutes by the type of tissue used-we distinguish autografts,allografts,and *** are also completely synthetic *** aim of our article was to summarize the current state of knowledge and to sum up all the clinical applications of bioengineered materials in the periocular *** are only a few scientific articles about this topic and lack of prospective randomized studies aimed on use of bioengineered materials in periocular ***,there are many articles describing successful case reports or case reports *** to literature,bioengineered materials are the most commonly used in big traumas or large surgical defects,especially in oculoplastic tumour *** dermal substitutes are not frequently used in the periocular *** substitutes are useful,when it is not possible to close the defect with any other conventional surgical technique.

关键词： Periocular surgery bioengineered material oculoplastic surgery autograft allograft xenograft

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Socket discomfort in anophthalmic patients-reasons and therapy options

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Annals of Eye Science 2020年第4期5卷 50-56页

作者： alexander c.rokohl Marc Trester Yongwei Guo Adam Kopecky Ming Lin Vladimir Kratky Ludwig M.Heindl Department of Ophthalmology University of CologneFaculty of Medicine and University Hospital CologneCologneGermany Trester-Institute for Ocular Prosthetics and Artificial Eyes CologneGermany Eye center Second Affiliated HospitalSchool of MedicineZhejiang UniversityHangzhouChina Ophthalmology clinic University Hospital OstravaOstravaCzech Republic Faculty of Medicine University OstravaCzech Republic Department of Ophthalmology Ninth People’s HospitalShanghai Jiao Tong University School of MedicineShanghaiChina Department of Ophthalmology School of MedicineQueen’s UniversityKingstonCanada center for Integrated Oncology(cIO)Aachen-Bonn-cologne-Dusseldorf CologneGermany

A smooth and timely fitting of a visually appealing,custom-made eye prosthesis after the loss of an eye is not only essential from a cosmetic point of view but above all facilitates good social and psychological *** glass prostheses must be replaced at least once a year,PMMA prostheses polished once a year and renewed every five *** children,especially in growth phases,the fit of the prosthesis should be checked at least every six months and adjusted,if *** and ophthalmologists should determine an individual cleaning procedure together with the patient,which depends on both the prosthesis material and external *** such as allergic,giant papillary,viral,and bacterial conjunctivitis or even blepharoconjunctivitis sicca must be detected and treated at an early stage to avoid discomfort and to maintain the ability of prosthesis *** the case of inflammation-induced shrinkage of the conjunctival fornices or post-enucleation socket syndrome,surgical interventions are *** summary,an early supply with an eye prosthesis,adequate treatment of complications,and attention to psychological aspects,form the basis for a successful long-term rehabilitation of anophthalmic patients.

关键词： cryolite glass PMMA prosthetic eye eye prosthesis anophthalmia

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Enhancing 3D Reconstruction Accuracy of FIB Tomography Data Using Multi‑voltage Images and Multimodal Machine Learning

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Nanomanufacturing and Metrology 2024年第1期7卷 48-60页

作者： Trushal Sardhara alexander Shkurmanov Yong Li Lukas Riedel Shan Shi christian J.cyron Roland c.Aydin Martin Ritter Institute for continuum and Material Mechanics Hamburg University of TechnologyHamburgGermany Electron Microscopy Unit Hamburg University of TechnologyHamburgGermany Institute of Materials Physics and Technology Hamburg University of TechnologyHamburgGermany Institute of Materials Mechanics Helmholtz-Zentrum HereonGeesthachtGermany Research Group of Integrated Metallic Nanomaterials Systems Hamburg University of TechnologyHamburgGermany Institute of Material Systems Modeling Helmholtz-Zentrum HereonGeesthachtGermany

FIB-SEM tomography is a powerful technique that integrates a focused ion beam(FIB)and a scanning electron microscope(SEM)to capture high-resolution imaging data of *** approach involves collecting in-plane SEM imagesand using FIB to remove material layers for imaging subsequent planes,thereby producing image ***,theseimage stacks in FIB-SEM tomography are subject to the shine-through effect,which makes structures visible from theposterior regions of the current *** artifact introduces an ambiguity between image intensity and structures in thecurrent plane,making conventional segmentation methods such as thresholding or the k-means algorithm *** study,we propose a multimodal machine learning approach that combines intensity information obtained at differentelectron beam accelerating voltages to improve the three-dimensional(3D)reconstruction of *** treatingthe increased shine-through effect at higher accelerating voltages as a form of additional information,the proposed methodsignificantly improves segmentation accuracy and leads to more precise 3D reconstructions for real FIB tomography data.

关键词： Multimodal machine learning Multi-voltage images FIB-SEM Overdeterministic systems 3D reconstruction FIB tomography

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